Double-unit cord blood not superior to single unit in transplantation for leukemia, MDS

The use of a double unit of unrelated cord blood did not significantly decrease transplantation failure in children and young adults with acute leukemia or myelodysplastic syndrome compared with using a single unit with adequate cell dose, according to the results of a randomized trial.

Further, use of a single unit resulted in lower transplant-related mortality.

As such, a single unit of unrelated cord blood should remain the standard of care for patients undergoing transplantation, and double-unit cord blood should be reserved for patients who lack adequate cell-dose containing cord blood.

“During the last 2 decades, cryopreserved unrelated cord blood (UCB) has become an alternative stem cell source for patients who need hematopoietic stem cell transplantation and lack an HLA–identical donor,” Gérard Michel, MD, of the department of pediatric hematology and oncology at Hôpital d’Enfants de la Timone in Marseille, France, and colleagues wrote. “However, UCB units contain a limited number of hematopoietic cells and, as early as in the first reported clinical studies, this cell dose was identified as a major predictive factor for posttransplant outcome. Transplantation of two UCB units has been proposed to augment the transplanted cell dose with very promising early results.”

Michel and colleagues designed a prospective study to compare the use of single UCB vs. double UCB in children and young adults with acute leukemia in remission or myelodysplastic syndrome.

The initial intent-to-treat population included 151 children and young adults in France who had at least two 4 to 6 HLA–identical UCB, with more than 3x10⁷ nucleated cells per kilogram for the first and more than 1.5x10⁷ for the second. The researchers randomly assigned these patients to single- (n = 74) or double-unit (n = 77) transplantation.

The majority of the cohort (79.5%) were aged younger than 18 years, and the majority of patients (59.6%) had acute lymphoblastic leukemia. The remaining 40.6% had acute myeloid leukemia or myelodysplastic syndrome.

However, 14 patients (single, n = 6; double, n = 8) relapsed between randomization and their planned graft; the final analysis included data from the remaining 137 patients.

The 2-year cumulative incidence of transplantation strategy failure — including transplant-related mortality, engraftment failure and autologous recovery — served as the primary outcome measure.

The use of double UCB did not significantly decrease transplantation strategy failure over single-UCB (23.4 ± 4.9% vs. 14.9 ± 4.2%).

Further, patients assigned to single UCB transplantation had lower rates of transplant-related mortality (5.9 ± 2.9% vs. 11.6 ± 3.9%), as well as higher 2-year DFS (68.1 ± 6% vs. 67.6 ± 6%) and survival after transplantation (74.8 ± 5.5% vs. 68.6 ± 6%).

Similar hematologic recovery time occurred in both groups, including median time to neutrophil recovery (24.8 ± 1 days vs. 23.5 ± 0.8 days) and 60-day probability of recovery (92.6 ± 3.3% vs. 94.2 ± 3%).

Although the 2-year cumulative incidence of relapse did not statistically differ, relapses occurred earlier in the single-UCB group (median, 164.9 ± 17.6 days vs. 282.4 ± 48 days; P = .04).

Conversely, although overall incidences of acute and chronic graft-versus-host disease did not differ, chronic GVHD was more frequently extensive after double UCB transplantation (median, 31.9 ± 5.7% vs. 14.7 ± 4.3%; P = .02).

An exploratory subgroup analysis showed a significantly lower relapse risk among patients who received double-UCB transplantation and total body irradiation without antithymocyte globulin (7.1 ± 4% vs. 21.9 ± 6.6%; P = .05). The relapse risk did not differ by treatment arm or other conditioning regimens.

“We conclude that double-unit strategy proved ineffective at improving the outcome of a UCB transplant when a single cord has an adequate cell dose,” Michel and colleagues wrote. “Future approaches to facilitate engraftment and to improve patient survival may include better HLA matching with high-resolution typing of 8 instead of 6 loci, as well as in vivo cord blood priming or expansion.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures.